The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

Abstract

Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P = 0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

<p>Evaluation of Therapeutic Drug Monitoring in the Clinical Management of Patients with Rheumatic Diseases: Data from a Retrospective Single-Center Cohort Study</p>

“…TDM resulted in treatment changes in 22% patients with Crohn's disease, and in 37% of inflammatory bowel disease patients with secondary loss of response. 13,14 Similar results have been seen in a pediatric inflammatory bowel disease cohort. 15 Although dose reduction has been shown to be a feasible approach, such a proactive empirical approach in patients showing a good response has rarely been employed.…”

“…We identified an IFX trough level threshold around 2.8 mg/L for discriminating between future treatment failure and remission/low disease activity, in line with results for inflammatory bowel disease patients. 4,14,23 Accordingly, we adjusted our therapeutic ranges for IFX to 3-7 mg/L. Pouw et al found a correlation between disease activity and ADL trough levels, identifying a therapeutic window of 3-12 mg/L, while Keystone et al recommend a narrower interval, 5-8 mg/L.…”

Therapeutic drug monitoring was helpful in guiding the decision‐making process for children receiving infliximab for inflammatory bowel disease

“…The change in colour, from blue to yellow, was recorded using the spectrophotometry technique. The intensity of yellow colour was directly proportional to the concentration of the drug . A suboptimal infliximab serum level was defined as a level of less than 3.5 μg/mL.…”

“…The secondary loss of response could be related to the formation of antidrug antibodies (9)(10)(11)(12). Mitchell et al (2) concluded that immunogenicity to infliximab could occur in 11% of patients.…”

“…Infliximab, a partly human partially murine antitumour necrosis factor (TNF) antibody, has been proved effective in treating inflammatory bowel disease (IBD) . The role of anti‐TNF antibodies in the induction and maintenance of remission in IBD has been well established for several years .…”